The sulfonamides work because they are very similar to naturally occuring compounds in bacteria, the compound para-aminobenzoic acid (PABA).

Draw the structure of sulfonamide and PABA.

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Describe Folic Acid Metabolism.

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What is tetrahydrofolate?

Tetrahydrofolate is the key component in the cell.

What does tetrahydrofolate do?

(1) acts to carry methylene groups to transfer to various purins, pyrimidines (thymidine), and amindo acids.

Can purine synthesis still occur in the abscence of tetrahydrofolate?

yes, because under most situations, here is a supply of preformed purine. Therefore purine synthesis can still happen.

Can methionine synthesis still occur in the abscence of tetrahdydrofolate?

Methionine is present in the extracellular portions of our body so that there is not inhibition under most circumstances. However, if it is not ther in adequte supply, suflonamide may be bacteriocidal.

What des methionine do?

Methionine is a precursor to rpoeins and is a precursor to make dTMP (dTMP can also be made by thmidine)

Why doesn't it kill human cells too?

(1) We do not have this pathway to make THF
(2) We get folic acid in our diet.

What is the administration of sulfonamides?

Oral and topical.

How long do sulfonamides act?

short, immediate, and long-acting.

Are sulfonamides well-absorbed? And when is the peak concentration in blood?

It is well-absorbed and its peak concentration in blood is in 2-4 hours.

Sulfonamides are not recommended to be used for infants, pregnant women, or those nursing. Why not?

Sulfonamides bind to albumin displacing billirubin which then crosses the BBB and in newborns will cause kernicterus which is characterized by ataxia and involuntary movement. The billirubin binds to the basal ganglia in the subthalamic nucleus in the brain.

How is sulfonamide metabolized?

It is metabolized by the liver by N4 acetylation.

How is sulfonamide excreted?

Both the acetylated form and the non-acetylated form are excreted in te kidney. It is concentrated in thekidneys and as a result of excretion, urin is concentrated.

What are the uses for sulfonamide?

(1) Uncmplicated, acute urinary tract infections cuased by susceptible gram negative bacilli such as E. coli, klebsiella, proteus mirabilis, and vulgaris, and the gram positive staph Aureus.
(2) It is also used for nocoardiosus or pulmonary abscesses.
(3) It has been used as an alternative to other types of infections (such as nocardia, trachoma cuased by chlamydia trachomatis, or neisseria meningitis) but these are the main uses.

(1) Middle ear infections in children
(2) Resistant malaria
(3) melthicillin-resistant Staph. aureus
(4) Gram negative bacilli such as providencia, Serratia, Shigella, Brucellosis, Cholera.
It has the very important use for treating pneumocystis cariniae.

What are the toxicities of sulfamethoxazole-trimethoprim?

Similar toxicities as sulfonamides -
(1) GI disturbances
(2) Hyersensitivey
(3) Stephen-Johnson Syndrome
(4) Hemolytic Anemia if you have a G-6-phosphatase deficiency)
*** should not beused in children under 2 months of age, pregnant women or nursing mthers.